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Advanced Reproduction
Short Course 2000
FOAL IMMUNOLOGY
Lecture Notes
Darien J. Feary
Introduction
 | Failure of passive transfer of
immunity – the single most important condition predisposing the newborn
foal to developing potentially life-threatening infections. |
| Two other disorders of neonate that
relate to problems with immune system that develop at or near time of birth;
Neonatal Isoerythrolysis and Combined Immunodeficiency. These are relatively
uncommon disorders, but no less important. |
| Essential to recognize these
immunological disorders early to enable prompt and effective prevention,
treatment and management. |
The Immune System
| Basic principles of the horse’s
immune system – the microscopic defense system of the body. Enables the
body to target and destroy invading organisms that it is exposed to every
day, prevent infections from becoming established, respond to an infection
and enable the body to recover. |
| Anything that is foreign to the body
and can potentially cause disease we call and ANTIGEN – can be bacteria,
fungi, viruses, parasites, toxins, etc. |
| ANTIBODIES are part of the immune
system that combat foreign antigen invasion by binding to and destroying it. |
| Antibodies are essentially large
proteins, also called IMMUNOGLOBULINS (Ig). These terms often used
synonymously. There are various classes of Ig, with various roles in the
immune system depending on where they are predominantly found. The Ig of
primary concern in the newborn foal is IgG. |
Types of Immunity
| Basically the immune system can be
divided into two types; |
| Innate Immunity
– WBC’s and other cells which act non-specifically to
fight invading organisms. |
| Acquired immunity –
antibodies produced by specialized lymphocytes, and other specialized cells
which act specifically to target and destroy invading antigens. |
| As the name suggests, this type of
immunity is acquired, and proper development requires previous exposure to a
foreign organism, so that when exposed again, the body can mount a rapid and
more effective secondary response. |
| When immature, as it is in the
newborn foal, the acquired immune response is slow and essentially
ineffective. |
Foals Immune System
| The important aspects of the foals
immune system at birth that put it at a very high risk of developing life
threatening infections; |
| The newborn foal is what we call immunocompetant
at birth, that is, it has all the basic components of its innate
immunity that enable it to immediately respond to an antigenic challenge. |
| However, because of the nature of
the equine placenta (epitheliochorial- 6 layers) there is no transfer of
antibodies from the mare to the foal in the uterus. |
| As a result, the foal is born
without protective antibodies and has only its innate immune system, which
is also immature. |
| Therefore, it is vital to
provide some temporary protection against the many organisms the foal is
bombarded with on its emergence into the world. |
| This protection provided in the form
of maternal immunoglobulin in the colostrum of the mare. This passive
transfer of Ig, especially IgG is essential….what we call the passive
transfer of immunity. |
| The foal relies on this passively
derived protection against infection for the first 4 to 8 weeks of life. |
| Any delay or failure
in this vital transfer of immunity will increase the risk of foal developing
serious infections early in life. |
| Foals own active acquired immunity
begins to become functional from 4 weeks of age, in the normal foal, and
from about 2 weeks in the colostrum-deprived foal. It is not fully developed
until 4 to 5 months of age. |
| Maternally derived colostral
immunity in foal declines rapidly within first 3 to 4 weeks of life. |
| In optimal circumstances there is an
overlap of passive and active immunity. If passive transfer is inadequate,
the particularly dangerous period for foal is about 4 weeks of age. |
| So, how is this vital immunity
transferred? How can it fail? How do we tell it has failed before it is too
late? And how do we deal with the problem?? |
Colostrum
| The first ‘milk’ produced by the
mare. |
| Contains high levels of Ig,
particularly IgG, concentrated from the mare’s blood by the mammary gland
during the last 3-4 weeks of gestation. |
| Thick, yellow and sticky, because it
is high in proteins |
| Mare produces about 1-2L of
colostrums, but only ONCE during each pregnancy. It is rapidly replaced with
normal milk, low in Ig, within 12 hours after 1st suck. |
| Colostrum is important, not only
because it supplies essential immunoglobulins, but it is also a source of
calories, growth factors, WBC’s, laxatives and various factors which
enhance the intestinal absorption of colostral proteins. |
Absorption of Colostrum
| Absorption of colostral Ig carried
out by specialized cells in foals small intestine, which enable large
proteins, not normally absorbed due to there large size, to be taken up and
transferred to foals bloodstream, where they are detected at there highest
level at 6 hrs after ingestion. |
| These calls rapidly replaced by
mature intestinal cells. The ability of foal’s intestine to absorb Ig
declines rapidly and progressively over 24 hours, essentially gone by 12
hrs. |
| The loss of ability to absorb Ig
(gut closure) influence by various factors including foal stress, difficult
birth, lack of oxygen at birth, hypothermia etc. |
| In addition, while the gut is
permeable to colostrum, it is also permeable to bacteria and other organisms
in foal’s intestine. So, while increased intestinal permeability is good,
ideally we want the foal to ingest and absorb adequate colostrum as early as
possible to avoid intestinal infections. |
Failure of Passive Transfer
| FPT occurs when Ig from mare’s
blood does not reach protective levels in foal’s blood within a
certain period of time. |
| Level of IgG considered to be
protective depends on many factors relating to the foaling environment,
management, etc, but generally accepted that IgG level of serum of normal,
healthy foal is >8g/L (800mg/dl) within 24hrs after birth. |
| Complete FPT when foal serum IgG
level <2g/L |
| Partial FPT when levels of serum IgG
between 2 – 8g/L |
| However, the level of IgG that
protects the foal from infection very variable. Although strong correlation
between low IgG levels in colostrum-deprived foals and an increased risk of
serious infection, this is NOT to say that foal with IgG <2g/L WILL
develop serious infection after birth, or conversely, that foal with IgG
>8g/L WILL NOT get sick. |
| For our purposes, we can say that
FPT may be considered to have occurred when level of IgG in foal’s blood
is <8g/L, and that the foal requires some sort of temporary
supplementation with a source of IgG. |
Causes of Failure of Passive
Transfer
| There are many possible causes,
often don’t determine exact cause. |
| Can occur as a result of ANY
interference with sequence of events leading to effective transfer of IgG
from mare’s blood to mammary gland to foals blood within the critical time
period of 6-12 hours. |
| Can group various causes into
problems associated with; |
- Manufacture and secretion of
colostrum by MARE
- Ingestion and absorption of
colostrum by FOAL
| Mare Factors |
| The mare must concentrate the right
IgG from her blood, lactate at the time of foaling, produce
adequate volume of good quality colostrum…and allow
the foal to suck… What can go wrong?? |
| Premature Lactation
– or loss of colostrum.probably most common cause of FPT. Mare starts
running milk hours, even days before foaling. Limited amount of colostrum lost
and not produced again. |
| Why does this occur? Not really sure
of mechanism, but has been related to presence of placentitis, or placental
separation, or both, and also with twin pregnancies. |
| Failure of Milk let down
– opposite to premature lactation, less common. Lack of udder development,
pain from engorged udder, total lack of milk production due to certain plant
toxins. |
| Poor Colostral Quality
– important cause – quality of colostrum basically refers to level of IgG
in colostrum, which is very variable between individual mares, breeds, etc. |
| Good quality colostrum has IgG level
>30g/L, correlated to colostral specific gravity which is easily
measured, of >1.060 |
| Poor colostral quality occurs as
result of many factors, especially premature lactation, also premature
foaling, genetic defects in mares, aged (>15 yrs) mares, obese mares…also
found to occur more commonly in mares foaling early in season and in
Standardbred mares. |
| The Wrong IgG
– an effective acquired immune response can only be mounted if there has
been previous exposure to antigen…if foal born in different environment to
that which mare has been exposed to then she does not concentrate and transfer
protective IgG to foal in colostrum. |
| So, don’t
move mares to a different environment <4-5 weeks prior to foaling. |
| Prepartum mare immunization,
also very important…within a reasonable time to allow sufficient antibody
production against specific antigens and concentration into colostrum (covered
in Stacy’s Preventative Reproductive Medicine lecture) |
| Finally, mare can prevent foal
from sucking i.e., nervous maiden mares, rejection, aggression
mismothering. |
Foal Factors
| Normal foals stand and suck within 1
to 3 hours of birth. |
| Anything preventing foal standing and
sucking can potentially be a cause if FPT, eg, weak, premature foals, ‘dummy’
foals, deformed, bent-leg foals, sick foals, etc. |
| Premature gut closure – can occur
due to foal stress, disease, intestinal damage, and administering anything
other than colostrum orally before gut closure (Do not give normal milk to
foals before colostrum!) |
Diagnosis of FPT
| How do we tell foal has inadequate
protective IgG before foal gets sick and its too late? |
| Important to remember FPT has no
primary symptoms, so critical to identify these foals before they
develop obvious signs of infection. |
| On stud farms foaling numbers of
mares need simple,
effective, rapid and cheap method of diagnosis. |
| Subjective criteria –
identify high risk foals based on history of mare running milk, difficult
foaling, weak, deformed, dummy foals, old, obese mares, etc. |
| Testing Colostral quality –
using colostrometer to measure specific gravity of colostrum, if s.g<1.060
then foal serum IgG <5g/L. But disadvantage is must obtain colostral sample
immediately after foaling and before first suck. Advantage is
early enough to supplement foal with alternative source of colostrum. |
| Measuring Foal Serum IgG levels –more
common method of testing on stud farms. Can be measured as early as 6-12 hours
after first suck, but more reliable 18-24 hours. Glutaraldehyde Coagulation
Test most common, simple…is 0.5mls foal serum placed in vial clotted within
10 mins then IgG level >8g/L. Assessed at 5-10 min intervals, if fails to
clot within 60 mins then complete FPT. Advantage is accurate and easier to
obtain sample in time period, but too late to supplement with colostrum as gut
closure has occurred. |
Treatment and Prevention of FPT
| Best treatment for FPT foals is
PREVENTION…early detection and early supplementation is the key! |
| Form of supplemental IgG depends
on age of the foal. |
| Foal <12 hours old
– give ORAL COLOSTRUM. Colostrum is the fluid of choice and the best
preventative, if given early enough, as its natural and provides all other
beneficial factors discussed earlier. It is easy to administer via stomach
tube or bottle. If from mares from same farm has right IgG’s. |
| Need to give at least 1L, up to 2L
for average 45kg foal, in small meals of 200-300mls/feed. |
| Colostrum can be fresh or frozen.
Possible to collect up to 250mls from mare with newborn foal at foot,
collect from least sucked teat. Or can thaw frozen colostrum from colostrum
bank. |
| Thaw colostrum slowly in warm water
<39 degrees…DO NOT MICROWAVE!! This destroys essential proteins. |
| Colostrum should be measured prior
to freezing and be of good quality, i.e. s.g >1.060. |
| Colostrum can be stored for 1 year
safely, provided not thawed then re-frozen. |
| PLASMA can also be administered
orally as source of IgG, but is more expensive and doesn’t provide other
important factors found in colostrum. |
| Bovine (cattle) colostrum can also
be given if desperate!! Apparently goat colostrum is also suitable! |
| Foal >12 hours old
– give IV PLASMA transfusion. Need to give IgG directly into bloodstream as
gut has closed. This method more time consuming, need IV line, takes 30-40
mins to run in 1L plasma, risk of transfusion reaction, requires veterinarian,
more expensive and lack other factors in colostrums. |
| However, if done right it is very
effective in treating FPT, the earlier the better. |
| Can use commercial sources of
plasma, safe, good quality. In general, need to give 1-2L plasma, may need
to give repeat transfusions to achieve final serum IgG levels of >8g/L,
depending on initial IgG level. |
| Sick foals often require more, as
IgG metabolized more rapidly…good idea to repeat IgG test to ensure
adequate IgG levels. |
Prevention and Management
| Good management = prevention. |
| Some studs have more problems with
FPT, most likely reflection of management. |
| Early detection…develop system of
identification that works for the farm. Get to the problem early! |
| Supervision…attendance at foaling.
Don’t need to interfere, but be there if needed. |
| Hygiene…reduce number of antigens
foal is exposed to at birth. |
| Reduce stress…of mare and foal at
birth. Do not transport prior to foaling, immunize mare, etc. |
Take home messages:
| Normal foals suck with 1 to 3 hours
of birth…identify foals
at risk and test colostrum or foal serum IgG… |
| Supplement early,
preferably with colostrum before 12 hours after birth… |
| Don’t wait
until foals get sick with obvious signs... |
| Management,
management, management….plan before season starts! |
Neonatal Isoerythrolysis (NI)
Introduction
| Uncommon but serious and potentially
fatal condition of newborn foal must be recognized early. |
| NI is essentially a disorder of
blood group incompatibility between foal and mare, inherited from the
stallion. Involves destruction of foal’s red blood cells by mare’s
immune system AFTER ingestion of antibodies in mare’s colostrum. |
| Occurs only when particular set of
circumstances met i.e., foal inherits particular Aa or Qa blood type from
stallion, exposure of mares blood to foals blood, mares immune system
recognize as foreign antigens, time to mount effective secondary immune
response and ingestion of anti-RBC antibodies by foal. |
| Mixing of maternal and foal blood
can occur late in gestation, or more commonly during foaling process.
Therefore condition more often seen in multiparous mares as first foal
usually not affected, need time to mount immune response, antibodies
concentrated in colostrum and ingested by subsequent foals. |
| If primary exposure during
ingestion, then first foal may be affected. |
Clinical Signs
| NI foals are NORMAL AT BIRTH. After
ingesting colostrum become progressively weaker, depressed as RBC’s
rabidly destroyed when antibodies reach foals bloodstream. |
| Can occur from 12 hours to 5 days
after first suck, depending on level of antibodies ingested. The more rapid
the onset, i.e. <24 hours, the poorer the prognosis for survival. |
| Affected foals mucous membranes
initially appear anemic (pale) and then yellow as destroyed RBC’s are
metabolized. Some foal’s die before get to the yellow stage. |
| Foals may also show difficulty
breathing, have red discoloured urine, eventually seizures, coma and die. |
Diagnosis
| Very important to detect early…typical
signs of weakness, depression, pale or yellow foals that are NORMAL at
birth, suck vigorously, then deteriorate after ingesting colostrum. |
| History of mare with previous NI
foal. |
| Specialized tests to definitively
diagnose condition by detecting mare anti-RBC antibodies, but don’t have
time to wait for results before treating. |
Treatment
| Prevent further ingestion of
colostrum by foal…muzzle, feed supplemental colostrum from unaffected mare
for at least 24 hours. Milk mare regularly and discard her colostrums. |
| Supportive care very important. Keep
warm, minimize stress, nutrition, maintain blood volume, may need IV fluids
and/or blood transfusion if severely anaemic, antibiotics to prevent
secondary bacterial infections. |
Prevention
| If mare known to have antibodies or
previous NI foal, muzzle foal at birth for 24 hours, milk mare and discard
colostrum, give foal colostrum from another mare. Foal can go back onto mare
after 24 hours as gut has closed by this stage. |
Combined Immunodeficiency (CID)
Introduction
| A primary genetic disorder of
Arabian bred foals, results in a complete failure to produce necessary cells
to mount immune response (lack B and T-lymphocytes) |
| Low incidence, about 3% |
| An autosomal recessive trait,
carriers show no clinical signs but can pass on genes, incidence of 25%. |
Clinical Signs
| Generally non-specific, foals
develop persistent, recurring infections due to lack of acquired immune
system. Most commonly respiratory tract infections with nasal discharge,
coughing, breathing difficulties. Or may have signs of any other infection
elsewhere in body. |
| Most important clinical sign is
affected foals are normal at birth and generally do not show signs of
infection for days, weeks or even months. Foals may temporarily improve with
treatment of infection, but not long term and affected foals usually die
within 6 months. This is distinguished from FPT and NI foals, which develop
clinical signs rapidly, and soon after birth. |
Diagnosis
| Based on clinical signs, age of
foal, history and breed. |
| Blood test shows very low lymphocyte
count and absence of IgM |
| Post mortem shows very undeveloped,
small organs involved in immune system, i.e., spleen, thymus, lymph nodes. |
Treatment
| No recommended treatment. Prevent
disease by not breeding with known affected individuals, by affected
offspring, and testing for carriers. |
THE END…Happy
Foaling!! |
